RSV is one of the most common cause of lower respiratory tract infections in infants and small children world wide. There is yet no vaccine licensed. Several types of vaccines are currently under development and many live attenuated and mutant vaccine strains seem to be promising candidates at present. However, one of the safety issues with live attenuated and mutant vaccines is the possibility of reversion to wild type phenotype due to genetic instability of the attenuating mutations. Any additional molecular markers that can distinguish between the wild-type and vaccine strains would be useful to screen for the revertants. The ability to produce Interferons (IFNs) and the sensitivity to IFNs can serve as molecular markers for this purpose. With this goal in mind, initiallly we are studying the ability of the wild-type RSV strain A2 to produce different IFNs and its sensitivity to IFNs in relevant cell lines such as those derived from human lungs. Similar studies will be conducted with three attenuated temperature sensitive (Ts) mutant strains of RSV strain A2 to characterize their differences to be serve as molecular markers. Vaccine safety is one of the most important goals of the CBER mission. As new vaccines are developed, new types of safety issues arise. As live attenuated mutant vaccines are developed, there is the possibility of genetic instability and reversion to wild -type phenotype that is not acceptable for vaccination. This research program provides information relevant to the standardization of all live, attenuated mutant RSV vaccines relative to their wild type parent, using IFN synthesis and sensitivity to IFNs as the markers. Results and knowledge gained will be useful for establishing the correlates between the attenuating phenotype and the described markers. This information woulde be useful in the review of INDs and license applications and to set lot release testing criteria needed for qualification of commercial vaccines.